Mpox is clinically similar to smallpox. Prior to the 2022 outbreak, skin lesions on any part of the body shared the same stage of development.

In the 2022 global outbreak, atypical clinical presentations include skin lesions starting in the genital, perianal, or oral regions, lesions localized to a specific anatomic site, and lesions being in different stages of progression on a specific anatomic site (eg, vesicles and pustules existing side-by-side).

Unlike smallpox, lymphadenopathy is common in mpox.